Single Cell Omics has become a new frontier and represents the unique convergence of technology and biology. In this SBIR project, Newomics Inc. proposes to develop a new platform for single cell proteomics and metabolomics of circulating tumor cells (CTCs). We will develop a groundbreaking and fully-integrated Omics-chip to isolate CTCs and perform high-sensitivity and high-throughput mass spectrometry-based analysis of isolated single CTCs. In the Phase I, we propose to develop a multi-layer and multi-module CTCchip for isolation (enrichment, sorting, and selection) of single CTCs from human blood. We will develop and test the CTC-chips using CTC-spiked blood samples, and validate their performance using clinical samples from metastatic cancer patients. If our Phase I project is successful, in the future Phase II stage, we will develop Omics-chips by integrating CTC-chips with our breakthrough multinozzle emitter array (MEA) chips. Our Omics-chip will serve as a universal platform to enable single cell omics of rare and heterogeneous cells including CTCs. The biological/clinical lessons learned from Omics analysis of CTCs at the single cell level will help elucidate the metastatic initiation, development, and prognosis, thereby providing new strategies for personalized therapies and for circumventing drug resistance.